Ecstasy Linked to Hippocampal Damage, Imaging Study Shows

Findings May Explain Observation That Long-Term Users Experience Significant Memory Impairment

Fran Lowry

April 07, 2011

April 7, 2011 — Long-term users of the recreational drug ecstasy (3,4-methylenedioxymethamphetamine) may be prone to incurring hippocampal damage, putting themselves at risk for significant memory impairment, preliminary results from a new study suggest.

Other studies have shown that people who use ecstasy display significant memory impairments, although their performance on other cognitive tests is generally normal.

Despite these findings, there have been no structural human data, such as volume measurements, of areas of the brain that might be affected by the drug, senior study author Liesbeth Reneman, MD, from the Department of Radiology at the Academic Medical Center, Amsterdam, The Netherlands, told Medscape Medical News.

Accordingly, she and her team set out to investigate whether the hippocampal volume of long-term ecstasy users was reduced in comparison with healthy individuals who used a variety of other drugs but no ecstasy.

The study was published online March 28 in the Journal of Neurology Neurosurgery and Psychiatry.

Damage May Not Be Limited to Hippocampus

The investigators used previously acquired volumetric magnetic resonance imaging (MRI) scans to compare hippocampal volume in 10 males in their mid-20s (mean age, 25.4 years; SD, 2.1 years) who were long-term users of ecstasy with that of 7 healthy, similar-aged males (mean age, 21.3 years; SD, 3.9 years) with no history of ecstasy use.

Although the ecstasy users had used more amphetamine and cocaine, there were no significant differences between the 2 groups in recreational drug exposure, other than ecstasy. Both groups also drank alcohol regularly.

The men in the ecstasy group had not been using the drug on average for more than 2 months before the start of the study but had taken an average of 281 ecstasy tablets during the preceding 6.5 years.

The study found that the hippocampal volume in the ecstasy-using group was on average 10.5% smaller than the hippocampal volume in the control group (3.8 ± 1.6 mL vs 3.4 ± 4.4 mL; P = .032).

In addition, the overall proportion of gray matter was on average 4.6% lower in the ecstasy users (51.5% ± 1% vs 49.1% ± 2.4; P = .022) after adjusting for total brain volume, when analyzed using voxel-based morphometry.

"This indicates that the effects of ecstasy may not be restricted to just the hippocampus," Dr. Reneman noted.

First Investigation of Memory Performance

There have been several alerts about hippocampal damage with ecstasy, Dr. Reneman said.

"Studies have shown hippocampal swelling and subsequent atrophy in patients following ecstasy ingestion, there have been documented memory impairments in ecstasy users, and prospective studies have shown a decline in memory performance following even low exposure," she said.

Moreover, there have been animal and human studies demonstrating serotonin neurotoxic effects of ecstasy in the hippocampus, as well as correlations between memory impairment and hippocampal volume in users of methamphetamine, the related amphetamine derivative, she said.

"I was not so much surprised by our findings as I was by the fact that nobody had yet investigated this possibility because of the various studies on reduced memory performance in frequent ecstasy users and the well-known involvement of the hippocampus and memory function," said Dr. Reneman.

For now, the observed hippocampal volume loss can be regarded as an incidental finding, she said, "in the sense that hippocampal volume loss per se does not induce any health problems," she said.

The finding needs to be reproduced in larger, preferably prospective studies, she added.

"If the observation holds true, then our findings of hippocampal damage may better explain the memory deficits observed in ecstasy users."

Need for Replication

Commenting on this study for Medscape Medical News, Jean M. Bidlack, PhD, professor at the University of Rochester School of Medicine and Dentistry in New York, said the finding provides a structural basis for the memory impairment observed in ecstasy users.

"We now have preliminary evidence that the size of the hippocampus in chronic ecstasy users is smaller than it is in individuals who have not used ecstasy. The study now needs to be followed up with a larger study that enrolls a greater number of former ecstasy users," Dr. Bidlack said.

Dr. Reneman and Dr. Bidlack have disclosed no relevant financial relationships.

J Neurol Neurosurg Psychiatry. Published online March 28, 2011. Abstract

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